System for enriching a bodily fluid with a gas having automated priming capabilities

ABSTRACT

This invention discloses a modular system having a base module, a mid-section control module, and a display module for preparing and administering a gas-enriched bodily fluid. Gas-enrichment is achieved by a gas-enriching device which can be in the form of a disposable cartridge. During operation, the gas-enrichment device is placed in an enclosure within the control module to form a fluid pathway for extracorporeal circulation of the bodily fluid. An electronic controller manages the various aspects of the system and executes an automated method for priming the extracorporeal circuit.

FIELD OF THE INVENTION

The present invention relates generally to gas-enriched fluids and, moreparticularly, to a system that enriches a bodily fluid with a gas.

BACKGROUND OF THE RELATED ART

This section is intended to introduce the reader to various aspects ofart that may be related to various aspects of the present invention thatare described and/or claimed below. This discussion is believed to behelpful in providing the reader with background information tofacilitate a better understanding of the various aspects of the presentinvention. Accordingly, it should be understood that these statementsare to be read in this light, and not as admissions of prior art.

Gas-enriched fluids are used in a wide variety of medical, commercial,and industrial applications. Depending upon the application, aparticular type of fluid is enriched with a particular type of gas toproduce a gas-enriched fluid having properties that are superior to theproperties of either the gas or fluid alone for the given application.The techniques for delivering gas-enriched fluids also varydramatically, again depending upon the particular type of applicationfor which the gas-enriched fluid is to be used.

Many commercial and industrial applications exist. As one example,beverages may be purified with the addition of oxygen and carbonatedwith the addition of carbon dioxide. As another example, thepurification of wastewater is enhanced by the addition of oxygen tofacilitate aerobic biological degradation. As yet another example, infire extinguishers, an inert gas, such as nitrogen, carbon dioxide, orargon, may be dissolved in water or another suitable fluid to produce agas-enriched fluid that expands on impact to extinguish a fire.

While the commercial and industrial applications of gas-enriched fluidsare relatively well known, gas-enriched fluids are continuing to makeinroads in the healthcare industry. Oxygen therapies, for instance, arebecoming more popular in many areas. A broad assortment of treatmentsinvolving oxygen, ozone, H₂O₂, and other active oxygen supplements hasgained practitioners among virtually all medical specialties. Oxygentherapies have been utilized in the treatment of various diseases,including cancer, AIDS, and Alzheimer's. Ozone therapy, for instance,has been used to treat several million people in Europe for a variety ofmedical conditions including eczema, gangrene, cancer, stroke,hepatitis, herpes, and AIDS. Such ozone therapies have become popular inEurope because they tend to accelerate the oxygen metabolism andstimulate the release of oxygen in the bloodstream.

Oxygen is a crucial nutrient for human cells. It produces energy forhealthy cell activity and acts directly against foreign toxins in thebody. Indeed, cell damage may result from oxygen deprivation for evenbrief periods of time, and such cell damage can lead to organdysfunction or failure. For example, heart attack and stroke victimsexperience blood flow obstructions or divergence that prevent oxygen inthe blood from being delivered to the cells of vital tissues. Withoutoxygen, these tissues progressively deteriorate and, in severe cases,death may result from complete organ failure. However, even less severecases can involve costly hospitalization, specialized treatments, andlengthy rehabilitation.

Blood oxygen levels may be described in terms of the concentration ofoxygen that can be achieved in a saturated solution at a given partialpressure of oxygen (pO₂). Typically, for arterial blood, normal oxygenlevels, i.e., normoxia or normoxemia, range from 90 to 110 mmHg.Hypoxemic blood, i.e., hypoxemia, is arterial blood with a pO₂ less than90 mmHg. Hyperoxemic blood, i.e., hyperoxemia or hyperoxia, is arterialblood with a pO₂ greater than 400 mmHg, but less than 760 mmHg.Hyperbaric blood is arterial blood with a pO₂ greater than 760 mmHg.Venous blood, on the other hand, typically has a pO₂ level less than 90mmHg. In the average adult, for example, normal venous blood oxygenlevels range generally from 40 mmHg to 70 mmHg.

Blood oxygen levels also may be described in terms of hemoglobinsaturation levels. For normal arterial blood, hemoglobin saturation isabout 97% and varies only as pO₂ levels increase. For normal venousblood, hemoglobin saturation is about 75%. Indeed, hemoglobin isnormally the primary oxygen carrying component in blood. However, oxygentransfer takes place from the hemoglobin, through the blood plasma, andinto the body's tissues. Therefore, the plasma is capable of carrying asubstantial quantity of oxygen, although it does not normally do so.Thus, techniques for increasing the oxygen levels in blood primarilyenhance the oxygen levels of the plasma, not the hemoglobin.

The techniques for increasing the oxygen level in blood are not unknown.For example, naval and recreational divers are familiar with hyperbaricchamber treatments used to combat the bends, although hyperbaricmedicine is relatively uncommon for most people. Since hemoglobin isrelatively saturated with oxygen, hyperbaric chamber treatments attemptto oxygenate the plasma. Such hyperoxygenation is believed to invigoratethe body's white blood cells, which are the cells that fight infection.Hyperbaric oxygen treatments may also be provided to patients sufferingfrom radiation injuries. Radiation injuries usually occur in connectionwith treatments for cancer, where the radiation is used to kill thetumor. Unfortunately, at present, radiation treatments also injuresurrounding healthy tissue as well. The body keeps itself healthy bymaintaining a constant flow of oxygen between cells, but radiationtreatments can interrupt this flow of oxygen. Accordingly,hyperoxygenation can stimulate the growth of new cells, thus allowingthe body to heal itself.

Radiation treatments are not the only type of medical therapy that candeprive cells from oxygen. In patients who suffer from acute myocardialinfarction, for example, if the myocardium is deprived of adequatelevels of oxygenated blood for a prolonged period of time, irreversibledamage to the heart can result. Where the infarction is manifested in aheart attack, the coronary arteries fail to provide adequate blood flowto the heart muscle. The treatment for acute myocardial infarction ormyocardial ischemia often involves performing angioplasty or stenting ofvessels to compress, ablate, or otherwise treat the occlusions withinthe vessel walls. In an angioplasty procedure, for example, a balloon isplaced into the vessel and inflated for a short period of time toincrease the size of the interior of the vessel. When the balloon isdeflated, the interior of the vessel will, hopefully, retain most or allof this increase in size to allow increased blood flow.

However, even with the successful treatment of occluded vessels, a riskof tissue injury may still exist. During percutaneous transluminalcoronary angioplasty (PTCA), the balloon inflation time is limited bythe patient's tolerance to ischemia caused by the temporary blockage ofblood flow through the vessel during balloon inflation. Ischemia is acondition in which the need for oxygen exceeds the supply of oxygen, andthe condition may lead to cellular damage or necrosis. Reperfusioninjury may also result, for example, due to slow coronary reflow or noreflow following angioplasty. Furthermore, for some patients,angioplasty procedures are not an attractive option for the treatment ofvessel blockages. Such patients are typically at increased risk ofischemia for reasons such as poor left ventricular function, lesion typeand location, or the amount of myocardium at risk. Treatment options forsuch patients typically include more invasive procedures, such ascoronary bypass surgery.

To reduce the risk of tissue injury that may be associated withtreatments of acute myocardial infarction and myocardial ischemia, it isusually desirable to deliver oxygenated blood or oxygen-enriched fluidsto the tissues at risk. Tissue injury is minimized or prevented by thediffusion of the dissolved oxygen from the blood to the tissue. Thus, insome cases, the treatment of acute myocardial infarction and myocardialischemia includes perfusion of oxygenated blood or oxygen-enrichedfluids. The term “perfusion” is derived from the French verb “perfuse”meaning “to pour over or through.” In this context, however, perfusionrefers to various techniques in which at least a portion of thepatient's blood is diverted into an extracorporeal circulation circuit,i.e., a circuit which provides blood circulation outside of thepatient's body. Typically, the extracorporeal circuit includes anartificial organ that replaces the function of an internal organ priorto delivering the blood back to the patient. Presently, there are manyartificial organs that can be placed in an extracorporeal circuit tosubstitute for a patient's organs. The list of artificial organsincludes artificial hearts (blood pumps), artificial lungs(oxygenators), artificial kidneys (hemodialysis), and artificial livers.

During PTCA, for example, the tolerable balloon inflation time may beincreased by the concurrent introduction of oxygenated blood into thepatient's coronary artery. Increased blood oxygen levels also may causethe hypercontractility in the normally perfused left ventricular cardiactissue to increase blood flow further through the treated coronaryvessels. The infusion of oxygenated blood or oxygen-enriched fluids alsomay be continued following the completion of PTCA or other procedures,such as surgery, to accelerate the reversal of ischemia and tofacilitate recovery of myocardial function.

Conventional methods for the delivery of oxygenated blood oroxygen-enriched fluids to tissues involve the use of blood oxygenators.Such procedures generally involve withdrawing blood from a patient,circulating the blood through an oxygenator to increase blood oxygenconcentration, and then delivering the blood back to the patient. Thereare drawbacks, however, to the use of conventional oxygenators in anextracorporeal circuit. Such systems typically are costly, complex, anddifficult to operate. Often, a qualified perfusionist is required toprepare and monitor the system. A perfusionist is a skilled healthprofessional specifically trained and educated to operate as a member ofa surgical team responsible for the selection, setup, and operation ofan extracorporeal circulation circuit. The perfusionist is responsiblefor operating the machine during surgery, monitoring the alteredcirculatory process closely, taking appropriate corrective action whenabnormal situations arise, and keeping both the surgeon andanesthesiologist fully informed. In addition to the operation of theextracorporeal circuit during surgery, perfusionists often function insupportive roles for other medical specialties to assist in theconservation of blood and blood products during surgery and to providelong-term support for patient's circulation outside of the operatingroom environment. Because there are currently no techniques available tooperate and monitor an extracorporeal circuit automatically, thepresence of a qualified perfusionist, and the cost associated therewith,is typically required.

Conventional extracorporeal circuits also exhibit other drawbacks. Forexample, extracorporeal circuits typically have a relatively largepriming volume. The priming volume is typically the volume of bloodcontained within the extracorporeal circuit, i.e., the total volume ofblood that is outside of the patient's body at any given time. Forexample, it is not uncommon for the extracorporeal circuit to hold oneto two liters of blood for a typical adult patient. Such large primingvolumes are undesirable for many reasons. For example, in some cases ablood transfusion may be necessary to compensate for the bloodtemporarily lost to the extracorporeal circuit because of its largepriming volume. Also, heaters often must be used to maintain thetemperature of the blood at an acceptable level as it travels throughthe extracorporeal circuit. Further, conventional extracorporealcircuits are relatively difficult to turn on and off. For instance, ifthe extracorporeal circuit is turned off, large stagnant pools of bloodin the circuit might coagulate.

In addition to the drawbacks mentioned above, in extracorporeal circuitsthat include conventional blood oxygenators, there is a relatively highrisk of inflammatory cell reaction and blood coagulation due to therelatively slow blood flow rates and large blood contact surface area ofthe oxygenators. For example, a blood contact surface area of about oneto two square meters and velocity flows of about 3 centimeters/secondare not uncommon with conventional oxygenator systems. Thus, relativelyaggressive anticoagulation therapy, such as heparinization, is usuallyrequired as an adjunct to using the oxygenator.

Finally, perhaps one of the greatest disadvantages to using conventionalblood oxygenation systems relates to the maximum partial pressure ofoxygen (pO₂) that can be imparted to the blood. Conventional bloodoxygenation systems can prepare oxygen-enriched enriched blood having apartial pressure of oxygen of about 500 mmHg. Thus, blood having pO₂levels near or above 760 mmHg, i.e., hyperbaric blood, cannot beachieved with conventional oxygenators.

It is desirable to deliver gas-enriched fluid to a patient in a mannerwhich prevents or minimizes bubble nucleation and formation uponinfusion into the patient. The maximum concentration of solubilized gasachievable in a liquid is ordinarily governed by Henry's Law. At ambienttemperature, the relatively low solubility of many gases, such as oxygenor nitrogen, within a liquid, such as water, produces a lowconcentration of the gas in the liquid. However, such low concentrationsare typically not suitable for treating patients as discussed above.Rather, it is advantageous to use a gas concentration within a liquidthat greatly exceeds its solubility at ambient temperature. Compressionof a gas and liquid mixture at a high pressure can be used to achieve ahigh dissolved gas concentration according to Henry's Law, butdisturbance of a gas-saturated or a gas-supersaturated liquid byattempts to inject it into an environment at ambient pressure from ahigh pressure reservoir ordinarily results in cavitation inception at ornear the exit port. The rapid evolution of bubbles produced at the exitport vents much of the gas from the liquid, so that a high degree ofgas-supersaturation no longer exists in the liquid at ambient pressureoutside the high-pressure vessel. In addition, the presence of bubblesin the effluent generates turbulence and impedes the flow of theeffluent beyond the exit port. Furthermore, the coalescence of gasbubbles in blood vessels may tend to occlude the vessels and result in agaseous embolism that causes a decrease in local circulation, arterialhypoxia, and systemic hypoxia.

In gas-enriched fluid therapies, such as oxygen therapies involving theuse of hyperoxic or hyperbaric blood, delivery techniques are utilizedto prevent or minimize the formation of cavitation nuclei so thatclinically significant bubbles do not form within a patient's bloodvessels. However, it should be understood that any bubbles that areproduced tend to be very small in size, so that a trained operator wouldtypically have difficulty detecting bubble formation without theassistance of a bubble detection device. Unfortunately, known bubbledetectors are ineffective for detecting bubbles in an extracorporealcircuit for the preparation and delivery of hyperoxemic or hyperbaricblood. This problem results from the fact that the size and velocity ofsome bubbles are beyond the resolution of known bubble detectors.Therefore, micro bubbles (bubbles with diameters of about 50 micrometersto about 1000 micrometers) and in some instances macro bubbles (bubbleswith diameters greater than 1000 micrometers) may escape detection.

SUMMARY OF THE INVENTION

In one aspect, the present invention provides a gas-enrichment systemhaving an extracorporeal circuit for enriching a bodily fluid of apatient with a gas-enriched fluid. The system generally includes anenclosure configured for receiving a gas-enrichment device; a fluidpumping assembly for controlling fluid flow through the extracorporealcircuit; and a controller for automatic control of gas-enrichment andextracorporeal circuit operations. The gas-enrichment device has agas-enrichment chamber for enriching a physiologic fluid with the gasand a mixing chamber for mixing the gas-enriched physiologic fluid withthe bodily fluid of the patient. When loaded into the system, thegas-enrichment device and the system provide a fluid path for the bodilyfluid to circulate from the patient to the mixing chamber and back tothe patient. The controller is capable of controlling the pumpingassembly and the gas-enrichment device to perform an automated sequenceof actions to prime the gas-enrichment chamber with the physiologicfluid upon loading the gas-enrichment device, and to prime the fluidpath with the bodily fluid upon receiving a priming command from theuser.

In another aspect, the present invention provides a gas-enrichmentsystem having an extracorporeal circuit for enriching a bodily fluid ofa patient with a gas-enriched fluid. As in above, the system has anenclosure configured for receiving a gas-enrichment device, a pumpingassembly, and a controller. The gas-enrichment device has agas-enrichment chamber for enriching a physiologic fluid with the gasand a mixing chamber for mixing the gas-enriched physiologic fluid withthe bodily fluid of the patient. The pumping assembly includes a pumpfor controlling fluid flow through the extracorporeal circuit. Thecontroller provides automatic control for gas-enrichment andextracorporeal circuit operations. When the gas-enrichment device isloaded, the system and the gas-enrichment device, together, provide afluid path for the bodily fluid to circulate from the patient to themixing chamber. The system further includes one or more load cellsconfigured to monitor the pressure within the extracorporeal circuit,and a memory device for storing pump, oxygen, and cartridge operatingparameters.

In still another aspect, the present invention provides a method forpriming an extracorporeal gas-enrichment system useful for enriching abodily fluid of a patient with a gas-enriched fluid. The gas-enrichmentsystem includes an enclosure configured for receiving a gas-enrichmentdevice having a physiologic fluid chamber, a gas-enrichment chamber, anda fluid mixing chamber. The fluid mixing chamber of the gas-enrichmentdevice has a first inlet operatively connected to a draw tube forreceiving the bodily fluid from a patient; a second inlet for receivinga gas-enrichment fluid; a first outlet for releasing gas from thechamber; a second outlet operatively connected to a return tube forallowing the gas-enriched bodily fluid to exit the chamber, wherein saidreturn tube is coupled to a return clamp capable of stopping fluid flowin the return tube when closed; one or more level sensors for monitoringfluid levels in the chambers; and one or more pressure transducer formonitoring the pressure in the extracorporeal circuit. The method hasthe steps of: loading the gas-enrichment device into the system; primingthe physiologic chamber and the gas-enrichment chamber with aphysiologic fluid; and priming the extracorporeal circuit by effectingthe bodily fluid to flow through the circuit, wherein the bodily fluidenters the circuit from the draw tube, flows into the mixing chamber andthen exits through the return tube. The step of priming the physiologicchamber and the gas-enrichment chamber is performed by the systemautomatically upon loading of the gas-enrichment device. The step ofpriming the extracorporeal circuit is performed when the system receivesa priming command from a user.

Other aspects and advantages of the invention will be apparent from thefollowing description and the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a block diagram for an exemplary gas-enrichment system inaccordance with embodiments of the present invention.

FIG. 2A shows the perspective view of an exemplary modulargas-enrichment system in accordance with embodiments of the presentinvention, 2B shows the base module separated from the mid-section anddisplay modules.

FIG. 3 shows the back view of the modular gas-enrichment system in FIG.2.

FIG. 4 shows a screenshot of an exemplary user interface display inaccordance with embodiments of the present invention.

FIG. 5 shows a diagram illustrating the phase angle of the transceiversin a combination bubble detector/flow meter in accordance withembodiments of the present invention.

FIG. 6 shows a block diagram of an exemplary system controller inaccordance with embodiments of the present invention.

FIG. 7 shows a state diagram of an exemplary system software inaccordance with embodiments of the present invention.

FIG. 8 shows a front view of a portion of the mid-section module in thesystem of FIG. 2 with a detailed view of the cartridge housing.

FIG. 9 shows a front view of the complete mid-section module in thesystem of FIG. 2.

FIG. 10 shows a perspective view of the mid-section of the system inFIG. 2 with a detailed view of the fluid pump system.

FIG. 11 shows a schematics view of the pump locking mechanism in thesystem of FIG. 2.

FIG. 12A shows a perspective view of the display module in the system ofFIG. 2; 12B shows a key frame representation of the sequence of actionsrequired to activate the power lever.

FIG. 13 shows a perspective view of the gas-enrichment device (i.e. thecartridge) in the system of FIG. 2.

FIG. 14 shows a detailed schematics view of the gas-enrichment device inthe system of FIG. 2.

FIG. 15 shows a detailed schematics view of the check valve in thegas-enrichment device of FIG. 14.

FIG. 16 shows a detailed schematics view of the piston pump in thegas-enrichment device of FIG. 14.

FIG. 17 shows a detailed schematics view of the atomizer assembly in thegas-enrichment device of FIG. 14.

FIG. 18 shows a detailed schematics view of the mixing chamber in thegas-enrichment device of FIG. 14.

FIG. 19 shows a detailed schematics view of the vent valves in thegas-enrichment device of FIG. 14.

FIG. 20 shows a detailed schematics view from the bottom of thecartridge housing enclosure in the system of FIG. 2.

FIG. 21 shows a detailed schematics view from the top of the cartridgehousing enclosure in the system of FIG. 2.

FIG. 22 shows a perspective view of an infusion catheter in accordancewith embodiments of the present invention.

FIG. 23 shows a plane view of an exemplary extracorporeal circuit setupin accordance with embodiments of the present invention.

FIG. 24 shows an exploded view of an exemplary Cartridge Housingenclosure in accordance with embodiments of the present invention.

FIG. 25 shows a block diagram illustrating the algorithm for flow ratemeasurement in accordance with embodiments of the present invention.

FIG. 26 shows a block diagram illustrating the algorithm for bubbledetection in accordance with embodiments of the present invention.

DETAILED DESCRIPTION

One or more specific embodiments of the present invention will bedescribed below. In an effort to provide a concise description of theseembodiments, not all features of an actual implementation are describedin the specification. It should be appreciated that in the developmentof any such actual implementation, as in any engineering or designproject, numerous implementation-specific decisions must be made toachieve the developers' specific goals, such as compliance withsystem-related and business-related constraints, which may vary from oneimplementation to another. Moreover, it should be appreciated that sucha development effort might be complex and time consuming, but wouldnevertheless be a routine undertaking of design, fabrication, andmanufacture for those of ordinary skill having the benefit of thisdisclosure.

System Overview

While systems of the present invention are not limited to preparation ofany particular type of gas or bodily fluid, for the purpose ofillustration, the following discussion will use the preparation ofoxygen-supersaturated fluids and the administration of SuperSaturatedOxygen (SSO₂) Therapy as an example.

For the purpose of the present discussion, SSO₂ Therapy refers tominimally invasive procedures for enriching oxygen content of bloodthrough catheter-facilitated infusion of oxygen-supersaturatedphysiological fluid. These procedures generally are aimed at treatingthe culprit vessel of an acute myocardial infarction (AMI) aftersuccessful percutaneous intervention (PCI) with stenting has beenperformed.

In a preferred embodiment, a system for administering SSO₂ Therapygenerally includes three component devices: the main control system, theoxygen-enrichment device (i.e., the oxygenator), and the infusion device(e.g., an infusion catheter). These devices function together to createa highly oxygen-enriched saline solution called SuperSaturated Oxygen(“SSO₂”) solution. A small amount of autologous blood is mixed with theSSO₂ solution producing oxygen-supersaturated blood, and then deliveredto the targeted major epicardial artery via the infusion catheter.Typical duration of SSO₂ Therapy is about 90 minutes.

Starting with the main control system, FIG. 1 shows a block diagram thatillustrates the architecture of a system in accordance with embodimentsof the present invention. With reference to FIG. 1, systems inaccordance with embodiments of the present invention are generallyorganized into a number of key subsystems, including a Display subsystem3010 which typically comprises a display such as a LCD display 3011 forproviding a user interface to the system, a Power Supply subsystem 1010for providing power to the system, a Gas Supply subsystem 1020 forsupplying the system with a gas to be used in enriching the fluid, and aCartridge Control subsystem 2001 for automatic control of gas-enrichmentand other system operations. Although a detailed discussion of thegas-enrichment device will be provided later, it is important torecognize that while in this preferred embodiment the gas-enrichmentdevice is in the form of a cartridge, (hence the name Cartridge Controlsubsystem), it is not the only possible form for the gas-enrichmentdevice. Thus, a more descriptive term for this subsystem isGas-enrichment Control subsystem. However, for the purpose of thepresent discussion, the terms Cartridge Control subsystem andGas-enrichment Control subsystem will be used interchangeably.

Functionally, the Cartridge Control subsystem is the center piece of theentire system. As shown in FIG. 1, the Cartridge Control subsystemtypically comprises a controller 2080 for processing input informationand issuing commands to the various components of the system. In apreferred embodiment, the controller also incorporates a safetyinterlock block 2090 for monitoring and ensuring the system operateswithin safety parameters. The safety interlock may be implemented with alogic block such as field programmable gate arrays (FPGA).

The Cartridge Control subsystem 2001 also includes a fluid pump assembly2010 which typically comprises a pump 2011, a draw tube 2020, a pressuresensor 2040, a bubble detector/flow meter 2060, a return clamp 2070, areturn tube 2030, and a Cartridge Housing 2050. The Cartridge Housing2050 is configured to receive a matching Cartridge (i.e. thegas-enrichment device). Within the Cartridge Housing 2050 enclosure,various sensing, controlling, and interfacing mechanisms are providedfor use with the Cartridge.

A physiologic fluid supply 3020 is included to provide a physiologicfluid source to the system.

It will be understood by those skilled in the art that thisorganizational architecture is a conceptual architecture. Actualphysical implementation is a matter of design choice which may take onvarious physical forms. For example, FIG. 2A shows a preferredimplementation of a system in accordance with the system architecture ofFIG. 1. As shown in FIG. 2A, the system has a modular design comprisingthree removable modules, the base module 1000, the mid-section controlmodule 2000, and the display module 3000.

In the above particular embodiment, the body of the base module 1000 ismade up of a tubular chassis situated on a circular-shaped pedestal1001. A plurality of wheels 1002 mounted on the bottom of thecircular-shaped pedestal provide mobility for the system. The wheelshave a locking mechanism for keeping the wheels stationary. The basechassis houses certain electrical and mechanical components including abattery 1003 (not shown), a power supply 1004 (not shown), andconnectors for connecting the base module 1000 to the mid-section mainmodule 2000. FIG. 2B shows a configuration of the system in which thebase module is separated from the mid-section and display modules.

FIG. 3 shows the back-end of the system. A gas tank receptacle 1021 isprovided on the back side of the base module 1000 for receiving andhousing a standard “E-bottle” USP oxygen tank 1022. The oxygen tank 1022is mounted to the system via gas tank adapter 280.

The system is preferably sized to be convenient for use in a normal cathlab environment. While the system may be configured as a stationarydevice or a fixture within a cath lab, it is often desirable for variouscatheter-based devices to be mobile. Accordingly, in this example,wheels are provided to satisfy this contingency.

Although some of the electrical and/or mechanical components of thesystem may be housed in the base module 1000, these components may beplaced in alternate locations of the system as a matter of designchoice. To facilitate positioning of the system, a rail handle 2120 maybe coupled to the mid-section control module 2000 for directing movementof the system.

Each of the three modules may include doors or access panels forprotecting and accessing the various components housed therein. Forexample, FIG. 2 shows the mid-section control module as having a hingeddoor 2051 for enclosing the gas-enrichment device (i.e. the Cartridge)and access panel 2052 for covering the access window to the internalspace of the module.

Referring again to FIG. 1, an appropriate draw tube 2020, such as anintroducer sheath, is used to draw a bodily fluid (e.g. blood) from apatient. The drawing action is provided by the fluid pump assembly 2010.Specifically, the fluid pump assembly includes a pump 2011, such as aperistaltic pump. As the peristaltic pump 2011 mechanically produces adriving force along the flexible draw tube, fluid within the tube 2020is pumped in the direction towards the system. A combinationbubble-detector/flow meter 2060 is typically coupled to the patient'sreturn tube 2030. Feedback from the flow meter can be used with a fluidpump assembly 2010 to operate as an automatic extracorporeal circuitthat can adjust the r.p.m. (revolutions per minute) of the peristalticpump to maintain the desired blood flow as well as provide continuousmonitoring of operating parameters to ensure safety conditions are met.

The draw tube 2020 and/or the return tube 2030 may be sub-selectivecatheters. The construction of the return tube 2030 may be of particularimportance in light of the fact that the gas-enriched bodily fluid maybe gas-saturated or gas-supersaturated over at least a portion of thelength of the return tube. Therefore, the return tube 2030, inparticular, is typically designed to reduce or eliminate the creation ofcavitation nuclei which may cause a portion of the gas to come out ofsolution. For instance, the length-to-internal diameter ratio of thereturn tube may be selected to create a controlled pressure drop andlaminar flow characteristics from the oxygenation device to the patient.

As shown in FIG. 23, an infusion catheter (the infusion device) isconnected to the return tube for conducting the oxygen-enriched bloodback to the patient. The infusion catheter is not particularly limited.Any suitable infusion catheter known in the art may be advantageouslyused. Typically, the infusion catheter is sized to fit within a 6 Frenchguide catheter. Materials such as polyethylene or PEBAX(polyetheramide), for example, may be used in the construction of thecatheter. Also, the lumen of the catheter should be relatively free oftransitions that may cause the creation of cavitation nuclei. Forexample, a smooth lumen having no fused polymer transitions typicallyworks well.

In conventional extracorporeal circuits such as those used forheart-lung machines, the tubing and oxygenation device forming thecircuit must be primed with a relatively large volume of a biocompatiblefluid. As fluid flows through the circuit, which are generally lengthyand may have a tortuous fluid flow path, degassing, bubble formation orbubble trapping invariably results. Thus, additional measures must betaken to eliminate air bubbles from the circuit. For example,vacuum-based gas eliminator, or membrane-based bubble filters aretypically required in conventional extracorporeal lines and devices. Inthis regard, it is an advantage of the present invention that the fluidpath formed by the draw tube and the return tube do not require largevolume of fluid. More importantly, the fluid path provided has ageometry that is smooth and conducive to streamlined laminar flow,thereby reducing the risk of bubble formation due to turbulent flowconditions. As such, it should be noted that one advantageous feature ofthe present invention is that the fluid path may be configured tominimize bubble formation without requiring additional bubble-removingapparatus.

Exemplary geometric parameters that may affect the internal fluid flowpath bubble nucleation characteristics include the cross-sectional areaof the fluid stream, slope or gradient of path curvature, and surfaceroughness, but are not limited thereto. These parameters may be easilyincorporated in the modular design of an exemplary system of the presentinvention to achieve an anti-bubble forming fluid flow path geometry.For example, as mentioned above, turbulence between tubing connectionsmay have a real effect in reducing bubble formations. In general,straight-line geometries, uniform flow path diameter, and slow changingcurvatures are conducive to non-turbulent flows.

Turning our attention now to the gas-enrichment device, FIG. 1 showsthat the blood (bodily fluid) is to be pumped through the draw tube 2020into the oxygenation Cartridge (gas-enrichment device) 2100. Althoughvarious different types of oxygenation devices may be suitable foroxygenating the patient's blood prior to its return, the oxygenationCartridge of the present invention advantageously prepares anoxygen-supersaturated physiologic fluid and combines it with the bloodto enrich the blood with oxygen. Also, the oxygenation Cartridge 2100 isadvantageously sterile, removable, and disposable, so that after theprocedure on the patient has been completed, the cartridge may beremoved and replaced with another cartridge for the next patient.

The Cartridge may additionally incorporate an information recordingelement to record the patient's health information and procedural dataso that the oxygenation cartridge is individually customized to guardagainst operator error. Exemplary information recording elements mayinclude a barcode label, an RFID chip, a PROM, or any combinationsthereof. Other component features and advantages of the oxygenationcartridge 2100 will be described in great detail below.

For the purposes of understanding FIGS. 1-3, it is sufficient at thispoint to understand that the physiologic fluid, such as saline, isdelivered from a suitable supply, such as an IV bag 3020, to a firstchamber within the oxygenation Cartridge under the control of a systemcontroller 2080. A suitable gas, such as oxygen, is delivered from a gassupply, such as an oxygen tank 1022, to a second chamber within theoxygenation Cartridge. Generally speaking, the physiologic fluid fromthe first chamber is pumped into the second chamber and atomized tocreate an oxygen-supersaturated physiologic solution. Thisoxygen-supersaturated physiologic solution is then delivered into athird chamber of the oxygenation cartridge along with the blood from thepatient. As the patient's blood mixes with the oxygen-supersaturatedphysiologic solution, oxygen-enriched blood is created. Thisoxygen-enriched blood flows from the third chamber of the oxygenationcartridge into the return tube 2030 (not shown).

When the Cartridge is loaded into the main control system, itsoperational status can be monitored through the display. As shown inFIG. 1, The Display subsystem 3010 provides an access point to thehost/user interface of the system. The user interface is preferablyimplemented as a series of on-screen graphical displays such as thegraphical menu system shown in FIG. 4. The pressure in the return tubeare monitored by the system via, for example, a pressure sensor 2040coupled to the return line as shown in FIG. 1.

The patient connections of the draw tube and the return tube that coupleto the oxygenation device are shown in FIG. 23. In this exemplaryimplementation, a return pressure sensor, which is operatively coupledto the Cartridge Control subsystem, provides pressure readings to thecontroller 2080. The location of the pressure sensor is not particularlylimited so long as the pressure being measured correspond to the desiredmeasurement location. In some embodiments, it is envisioned that loadcells may be incorporated directed in the Cartridge Control subsystem soas to eliminated the need for external pressure transducers. Thisconfiguration will have the benefit of reducing the cost necessary inembedding or coupling pressure transducers to the external lines.

The system controller may also receive a signal from a level sensor thatmonitors the level of fluid within the mixing chamber of the oxygenationdevice to ensure that the oxygen-supersaturated physiological solutionis mixing with the patient's blood with little or no bubble formation.

The combination bubble-detector/flow meter 2060 represents anotheradvantageous feature of the present system. Several conventiontechniques are known in the art for measuring a flow rate of a liquidflowing in a conduit, pipe, or tube. These include thermal flow meters,coriolis force flow meters, differential pressure flow meters, andultrasonic flow meters. Generally, fluid flow meters sense one or moreparameters (e.g. volumetric or mass) of the flow that can be calibratedto correspond to the rate of fluid flow. In situations where a bubble ispresent in the fluid, the presence of the bubble may disrupt any type offlow meter. For ultrasonic flow meters, this is particularlyproblematic, especially for fluids having relatively slow flow rates(e.g. <1 ml/s). Thus, in conventional applications, fluid flowmeasurements are usually accompanied with an independent bubbledetection sensor to act as a quality control for flow rate measurements.The present invention uses a single ultrasonic probe to both detectbubbles and measure flow rate at the same time.

The combination bubble-detector/flow meter 2060 is typically positionedat the return tube 2030 to detect bubbles as they pass through thereturn tube to the patient. Again, as discussed in greater detail below,the system receives the signals from the ultrasonic probe and processesinformation regarding the nature of any bubbles that may be traveling inthe oxygen-enriched blood going back to the patient. In this embodiment,the bubble detector provides this information to the host/user interfaceso that information regarding bubbles in the effluent may be provided tothe user via the display 3011. The combination bubble-detector/flowmeter 2060 may also control or shut down the system in certaincircumstances as discussed in detail below.

As discussed above, the controller incorporates an interlock block 2090that communicates with many of the components of the system for variousreasons. The interlock block 2090 monitors the various components toensure that the system is operating within certain prescribed bounds.For example, the interlock block 2090 may receive information regardingdraw and return pressures from the pressure sensors, informationregarding fluid level in the mixing chamber from the level sensor, andinformation regarding the number and/or size of bubbles from the bubbledetector, as well as other information regarding the operating states ofthe various components. Based on this information, the interlock blockcan shut down the system should it begin to operate outside of theprescribed bounds. For example, the interlock block 2090 can engage thefluid pump 2011 on the draw tube 2020 and the return clamp 2070 on thereturn tube 2030 to stop flow of the fluid, as well as disable the bloodpump assembly 2010 and the system controller 2080 that controls theoxygenation cartridge 2100.

While the interlock block 2090 typically operates in this automaticfashion, a safety switch (e.g. an emergency stop switch 3050 shown inFIG. 2) may be provided so that a user can initiate a shutdown of thesystem in the same fashion even if the system is operating within itsprescribed bounds.

Any number of hardware implementations may be used to implement thesafety interlock. In this preferred embodiment, the safety interlock2090 is implemented using field programmable gate array chips (FPGA) andis incorporated together with the cartridge controller circuitry.

Another advantageous feature of the present inventive system is theautomated priming mechanism and the small volume of priming fluidrequired. Relative to conventional extracorporeal circuits, the systemhas a far smaller priming volume requirement, typically in the range of25 to 100 milliliters. Thus, a heater typically is not used with thesystem. However, if it is desirable to control the temperature of theincoming blood in the draw tube or the outgoing gas-enriched blood inthe return tube, an appropriate device, such as a heat exchanger, may beoperatively coupled to one or both of the tubes. Indeed, not only maythe heat exchanger (not shown) be used to warm the fluid as it travelsthrough the system, it may also be used to cool the fluid. It may bedesirable to cool the fluid because moderate hypothermia, around 30° C.to 34° C. has been shown to slow ischemic injury in myocardialinfarction, for example.

In this preferred embodiment, priming may be initiated by holding downthe priming switch 3040. When the priming switch 3040 is released,priming action is immediately stopped. Wet-to-wet connections of variousfluid tubings further reduce the priming requirement for theextracorporeal circuit and minimizes the formation of bubbles duringpriming.

The details of the devices and their various respective subsystems willnow be described with reference to the preferred embodiment asillustrated in the remaining figures.

The Display Subsystem and the Host/User Interface

Turning now to FIG. 4, a screenshot of an exemplary embodiment of thehost/user interface is illustrated. The host/user interface includes auser interface and a host interface. The user interface may include userinput mechanism such as buttons, switches, and knobs. To communicatewith the user, a display device, such as an LCD display, a CRT display,or a touch screen display may be used. As illustrated in FIG. 4, thedisplay 3011 may show graphical representation of “buttons” and“pointers” to indicate to the user that a corresponding operation may beinitiated by pressing the buttons as indicated. The display 3011 mayalso include information such as alarms/messages, status indicators,blood flow information, and bubble count. In addition, the display 3011may also provide instructional information to the user for guiding theuser in using the system.

Implementation of the Display subsystem may include a user input driverfor handling user inputs and a display driver for handling actualdisplay of the information. The user input driver transmits user inputsto an interface, such as an RS-232 interface. The RS-232 interface maycommunicate these user inputs to other portions of the system, such asthe system controller, the interlock system, the blood pump system, orthe bubble detector. The display driver communicates with a displaycontroller, which is also coupled to the RS-232 interface via a bus. Thedisplay controller receives updated information from the various otherportions of the system, and it uses this information to update thedisplay.

The host interface may also include various other capabilities. Forexample, the host interface may include a sound card to drive speakerson the user interface. In addition, a network adapter may allow the hostinterface to communicate with an external network, such as a LAN in thehospital or a remote network for providing updates for the system, e.g.,the Internet.

In the present preferred embodiment as shown in FIG. 2, the displaysubsystem is embodied in a modular casing. FIG. 12A shows a perspectiveview of the display module when detached from the rest of the system.The Display subsystem provides the main user interface components of thesystem, which preferably includes the power lever, the control buttons(including the emergency stop switch and the priming switch), and theLCD display for communicating with the user. An IV pole is also attachedto provide a structure for hanging saline solution bags.

Referring to FIG. 9, the display module is shown as already mounted onthe top of the mid-section control module. In this figure, the system'spower lever 2140 is located at the dividing line of the upper sectionand the mid-section. The power lever controls both the ON/OFF states ofthe entire system and also the OPEN/CLOSE states of the oxygen tank.

During operation, a user slidably moves the lever 2140 to the side ofthe system (the ON position) in order to turn on the system. FIG. 12B,from left to right, illustrates the sequence of actions undertaken by auser to turn the power of the system ON as well as opening the gas tank.This operation also reveals the transducer connecter jack for connectingthe pressure transducer to the controller. As a built-in safety feature,the system requires the user to first remove the transducer cable 2062from the jack 2061 before returning the lever to the OFF position beforethe power lever can be moved to the OFF position.

As mentioned above, the power lever serves the dual role of power supplyswitch and oxygen tank switch. The dual function may be achieved bycoupling a shaft to the oxygen valve so that sliding the lever from theOFF position to the ON position also rotates the shaft to turn on theoxygen tank.

Implementation of the user interface preferably comprises an electronicassembly including a personal computer (PC) based main circuit board(CPU), and a color liquid crystal display (LCD). The circuitry isembedded on a PCB (the display PCB). The display PCB is mounted withinthe modular display enclosure. The enclosure also houses the LCD.Component features of the user interface include the display PCB, thecontrol buttons, and the LCD Display.

The display PCB preferably uses a commercially available microprocessorthat provides the platform for the User Interface application softwarerunning a Linux-based operating system. This board communicates seriallywith the Cartridge Control subsystem.

The LCD screen displays the video output of the display PCB. A set ofcontrol buttons located around the display provide the input for userselection of application software. The display PCB provides additionalfunctionality, analog-to-digital conversion and digital input/outputcapability. The user interface application software uses thesefunctions.

The Power Supply Subsystem

The Power Supply subsystem 1010 is an electronic assembly that providesDC power to the various subsystems. The power supply 1011 receives powerfrom the AC mains or internal batteries. Component features of the PowerSupply subsystem 1010 may include: detachable power cord, applianceinlet receptacle with fuses and selection of 110-V or 220-V operation,isolation transformer, AC to DC power supply with fuse, battery withfuse, battery charger, and DC to DC power supplies, but are not limitedthereto.

The isolation transformer provides electrical isolation forpatient/operator protection. Batteries 1012 (not shown) are incorporatedfor backup power and system mobility. These batteries provide a minimumof one hour of operation when fully charged. When connected to AC Mains,the system automatically charges the batteries. The Power SupplySubsystem 1010 also includes specific DC power supplies that providefixed voltages to other subsystems.

Preferably, the Power Supply subsystem does not require software.

The Gas-Supply Subsystem

As discussed above, the system of the present invention may be used toprepare a number of different gas-enriched fluids. In this preferredembodiment, it is an oxygen-supply subsystem 1020 that provides oxygento the oxygenation Cartridge 2100. FIG. 3 shows an oxygen tank 1022loaded in the back of the system. The oxygen supply is a mechanicalassembly that provides regulated oxygen to the oxygenation cartridge.The oxygen supply uses pressurized oxygen from a medical grade E-bottle,which it regulates to 750+50 psig. Component features of the OxygenSupply include: E-bottle (yoke-type) connection, oxygen regulator with900 psi relief valve, bottle pressure gauge, and oxygen filter. Theoxygen tank is mounted to the system at the base module 1000 where anoxygen tank receptacle 2010 is provided. The oxygen tank is connected tothe system via an oxygen tank adaptor 2110 located at the bottom of themid-section control module 2000.

The oxygen supply mechanical hardware for the system is mounted on thetop plate of the Cartridge Housing (to be described below). This platecontains an oxygen port that automatically connects and seals to theCartridge's oxygen inlet upon placement of the Cartridge within theCartridge Housing. After the oxygenation Cartridge 2100 is inserted, theclosed door 2051 of the Cartridge Housing 2050 contacts an actuator thatpushes the port into contact with the top of the cartridge 2100. Whenthe door is opened, a spring retracts the port. This plate also containstubing for conducting gas flow to the cartridge regulated by a flowvalve mounted on the outside of the enclosure.

During operation, the regulator of the oxygen tank stays open to providea constant source of oxygen gas. Flow of the oxygen gas is regulated bythe oxygen flow valve which is a normally closed solenoid that isactuated by the Cartridge Controller.

A bottle pressure gauge 2130 is provided on the front panel of thesystem (see FIG. 2) to indicate the pressure of the oxygen tank. Arelief valve is also provided to protect the system in the event thatexcess pressure builds up in the system. A pressure transducer locatedwithin the oxygen supply (upstream from the oxygen port) monitors oxygenpressure in the Cartridge. The transducer provides an analog pressuresignal to the Cartridge Controller; this signal is measured andmonitored to ensure that the pressure is within the operational limits.

The oxygen supply preferably has a standard yoke-type CGA-840 fitting,which connects to the hospital-provided oxygen bottle (E-bottle). Onefull E-bottle contains sufficient oxygen to support more than 50 SSO₂Therapy procedures. In this preferred embodiment, the yoke is connectedto a brass pressure regulator manufactured by Tescom Corporation (ElkRiver, Minn.).

A pressure gauge on the side of the regulator inlet measures the oxygenbottle pressure; the bottle pressure must be greater than or equal to800 psig in order to initiate SSO₂ therapy. The regulator is protectedfrom particulate debris by an inlet filter. The single-stage pressureregulator is pre-set at 750+50 psig (no user adjustment is necessary).The regulator is locked so that adjustments cannot be made to thepressure setting without a tool. A relief valve set to 900 psig ismounted on the regulator to protect the outlet side from regulatorfailure. The hose connects to a bulkhead fitting where the oxygen supplyenters the system main enclosure. An in-line filter inside of the mainenclosure protects components downstream of field service connections(bulkhead fitting). The oxygen supply connects to the oxygen valve onthe cartridge control subsystem with a 1/16″ tube. Approximately 2.5 Lof oxygen gas (at standard temperature and pressure, STP) is necessaryto pressurize the cartridge, and less than 3 ml (STP)/min is neededduring SSO₂ Therapy administration.

Preferably, the oxygen supply subsystem does not require software.

The Cartridge Control Subsystem

Components of the Cartridge Control subsystem 2001 are mainly located inthe mid-section of the system. As shown in FIG. 1, components of thissubsystem may include the controller 2080, the Cartridge Housing 2050,the Cartridge 2100 (when loaded), the blood pump assembly 2011, thebubble detector/flow probe 2060, the pressure transducers 2040, and thereturn safety clamp 2070.

The controller is the electronic assembly that monitors and controls theoperation of the Cartridge during SSO₂ Therapy. It is made-up of amicroprocessor which executes control software. FIG. 6 shows a blockdiagram of the system controller. The electronics of the controller ispreferably implemented in a printed circuit board (PCB). The Cartridgecontrol PCB (shown in FIG. 6 as the main controller board) receivesdigital and analog signals from electronic components within the system.The Cartridge control PCB also monitors the power supply voltage.

The Cartridge control PCB controls the piston actuator and all solenoidsof the Cartridge controller mechanism. The Cartridge control PCBoperates the fans that ventilate the main enclosure. The PCB preferablyuses an 8051 microprocessor with software that controls the operatingstate of the system.

FIG. 7 shows a software state diagram of the control software. Thesoftware is automatically executed when the Cartridge Control subsystemis started. The control software provides ten different operatingstates, including: (1) Power On State; (2) Ready State; (3) Prep State;(4) Prime State; (5) Start Recirculation State; (6) SSO₂ Off State; (7)SSO₂ On State; (8) Shut Down State; (9) Administration State; and (10)Diagnostics Mode State. The lines and arrows connecting the variousdifferent states indicate the logical relationship and transitionbetween the connected states. This software system is preferablyimplemented in C++.

With reference to FIG. 7, when the system is first powered up, thesoftware first enters the Power On state (1), during which the systemruns a series of initialization tests such as testing the power supply,the internal watchdog timer, the DSP, etc. If a critical fault conditionis detected during power up, the system enters the Shut Down state (8)to shutdown the system. The Power On state also offers the option toenter the Diagnostics Mode (10) which allows the user to control aspecific part of the system with relaxed interlocks. Once power up issuccessfully executed, the system may enter into the Ready state (2).

The Ready state (2) is the state that performs Cartridgeloading/unloading. If system encounters critical error during loading orunloading of the Cartridge, the system enters the Shut Down state (8).User input is then required to clear the loading/unloading error andtake the system back to the Ready state (2). From either the Shut Down(8) or the Ready (2) state, user can interrupt the system to enter theAdministration state (10) in order to check system parameters andperform system administrative tasks.

After the cartridge has been loaded into the Cartridge Housing, the userhas spiked the saline IV bag, and the Transducer is connected to thesystem, the user can Prep the cartridge. The purpose of Prep state (3)is to check the Fill, Flush and Flow Valves, to saline prime the fluidpath in the high-pressure side of the cartridge, establish the minimumliquid level, and pressurize with oxygen. If system encounters criticalerror during Prep, the system enters the Shut Down state (8). Prep isfully automated after user initiation.

Upon user input, the system may enter the Prime state (4) to prime theextracorporeal circuit. During this state, the pump is activated so longas the priming switch 3040 is pressed. Patient blood is drawn into themixing chamber as the pump turns. Again, the Prime state (4) also offersthe option of taking the system into the Shut Down state (8) when acritical fault condition is encountered or when a user input to shutdownis received. All states following the prime state will have the sameoption of entering the Shut Down state (8) upon encountering a criticalfault condition or user input.

After the user makes wet-to-wet connection of the return tube to theinfusion device, the system enters the Recirculation state (5), duringwhich the pump continues to turn as the blood flow and return pressurestabilize. Complete circulation of fluid in the extracorporeal circuitis established during this state to finish the priming process.

When priming is completed, the system enters into the SSO₂ OFF state(6), during which circulation of the extracorporeal circuit is continuedwith no infusion of SSO₂ solution. Thus, the blood from the patient isonly diluted slighted with the un-oxygenated saline. This state alsoallows the option of detecting a non-critical fault condition such as aminor occlusion in the extracorporeal tubing. When such a non-criticalfault condition is encountered, the system may return to theRecirculation state (5) to re-establish proper extracorporealcirculation. If no fault condition occurs, the system will remain in theSSO₂ OFF state until user input is received to enter the SSO₂ ON state(7).

In the SSO₂ ON state (7), the system produces oxygenated saline, infusesthe oxygenated saline with patient's blood in the mixing chamber of theCartridge, and then return the oxygenated blood back to the patient. Thesystem will remain in this state until completion of the therapy, userinterruption, or a fault condition. Similar to the SSO₂ OFF state (6),the SSO₂O ON state (7) also allows the option of responding to a minornon-critical fault condition by returning the system back to theprevious state, thus avoiding unnecessary shutdown of the system.

This system software is preferably encoded in the controller circuitry'spersistent memory (FIG. 6) so that it will be available to the systemupon power up.

Also included in the controller circuitry 2080 is a safety interlocklogic block for monitoring and ensuring that system operates withinsafety parameters. The safety interlock 2090 is basically adecision-tree logic performed by a logic device implemented with a FieldProgrammable Gate Array (FPGA) chip, which is integrated on thecontroller PCB. The FPGA circuitry is live at start-up. The safetyinterlock 2090 continuously monitors inputs for events that requiretreatment stoppage or enable treatment. The safety interlock 2090 hasthe ability to disable all powered electronics in the system. Whencertain conditions occur, the safety interlock stops treatment bydisabling powered (24V) electronics, which automatically closes thereturn safety clamp 2070, stops the blood pump 2011, stops the piston2161, closes the fluid flow valve, closes the oxygen valve, anddepressurizes the cartridge 2100.

Exemplary function-disabling parameters monitored by the safetyinterlock may include signals such as: emergency stop engaged, out ofrange oxygen pressure transducer signal, out of range piston pressuresignal, temperature high or low signal, low system voltage signal, bloodpump encoder or motor failure, piston stall or encoder failure, pistontop and bottom flag failure, solenoid driver open-circuit or over-tempcondition, display failure or bubble detector failure, and otherrelevant parameters.

The safety interlock also has logic that enables functions within theCartridge Control subsystem 2001 based on monitored inputs. Forinstance, the pump head 2012 will not operate if the pump head is open.

Exemplary function-enabling parameters monitored by the interlock mayinclude: prime switch pressed, pump head open, cartridge door open,oxygen valve open, blood pump operating, cartridge detected, cartridgetransducer detected, and other relevant parameters.

In addition to the above mentioned inputs to the safety interlock, anumber of operating inputs may also be fed into the controller toinfluence system behavior, including inputs from the priming switch, andinputs from the emergency stop switch.

The priming switch is mounted to the display module. The user must pressand hold to start the pump motor and initiate blood flow.

The emergency stop (E-stop) switch is also mounted to the displaymodule. The cartridge controller disables all powered electronics (24VDC) upon manual actuation of the E-stop switch by the system user. TheE-Stop switch latches when pressed and must be manually disengaged.

It will be noted that one advantageous feature of the present inventionis the automated safety responses enabled by the controller/safetyinterlock. In conventional extracorporeal systems, occlusion in thefluid conduits such as tubes or catheters often occurs. Vigilantmonitoring by the human operator is often required to catch suchocclusion events and resolve the problem by manually stopping thesystem, removing the occlusion, and then restarting the systemregardless of the degree of the occlusion. This indiscriminate occlusionresolution procedure is both time consuming and labor intensive. Becausesystems of the present invention have relatively short extracorporealpath and built-in controller/safety interlock, it is possible for thesystem to monitor for occlusion events by monitoring changes in flowrate and/or fluid pressure, and response according to the level ofocclusion. For example, if the occlusion event is minor and temporary,the controller may respond by stopping SSO₂ solution infusion, allowingextracorporeal circulation to restore to normal level, and notify theoperator to restart SSO₂ solution infusion without requiring a completeshutdown of the system. In the event that the occlusion is a major andcontinuous, the controller may then respond by stopping SSO₂ solutioninfusion, shutting down extracorporeal circulation, and notify theoperator to fix the problem before restarting the extracorporealcirculation and SSO₂ solution infusion.

Referring to FIGS. 8-10, a modular jack 2061 located on the front of thesystem enclosure is provided for connecting the cartridge transducer tothe Cartridge Controller via a transducer cable 2062. During setup, thesystem user inserts the cartridge pressure transducer cable 2062 intothe modular jack on the front of the system main enclosure. The analogpressure transducer input from the Cartridge is monitored by theCartridge Controller subsystem 2001. The threshold for the blood mixingchamber pressure is set to 2000 mmHg (38 psig).

The Cartridge Housing is preferably an anodized aluminum enclosure. Thishousing provides a receptacle for the oxygenation Cartridge. As shown inFIG. 8, the housing assembly is embedded in the mid-section main controlmodule 2000.

Referring to FIG. 24, the housing is formed by a receiver block 2049 forreceiving the oxygenation Cartridge, a top plate 2055, a bottom plate2056, and a door 2051.

Referring back to FIG. 8, pulling the door handle 2054 down and forwardopens the door when it is unlocked. Within the housing, an LED indicatorlight 2053 indicates the locking state of the door. When the door isunlocked and ready to be opened, the indicator is turned on. After thedoor is opened, the user may insert the oxygenation Cartridge 2100 intothe Cartridge Housing compartment 2050. Slots in the Cartridge Housingenable passage of the draw tubing, return tubing and IV tubing. TheCartridge 2100 is automatically aligned with all mechanical and sensorinterfaces within the Cartridge Housing 2050 when the housing door 2051is closed. The pressurized chambers of the disposable Cartridge 2100 areenclosed within the Cartridge Housing 2050. The Cartridge Housing 2050works in conjunction with the Cartridge 2100 during operation. It has amotorized piston actuator that operates the Cartridge piston anddelivers saline from an IV bag. The Cartridge Housing also has a set ofneedle value actuators to control the flow of liquid through theCartridge, and vent valve actuators to depressurize the Cartridge oxygenchamber and blood mixing chamber.

The piston actuator may be comprised of a piston ram, ball screw,stepper motor, stepper motor encoder, limit switches, and load cell. Thepiston ram is slotted to engage a key on the cartridge piston when thecartridge is installed into the cartridge housing. The ball screwattaches stepper motor to the piston ram; it converts the rotary motionof the stepper motor into linear motion needed to operate the pistonram. The stepper motor has a rotary output that is reduced in speed andincreased in torque by a gearbox. The stepper motor is driven by astepper motor controller. The stepper motor may also include an opticalencoder to detect motor speed and direction.

Two slotted IR sensors are used to detect the top and bottom position ofthe piston ram. A load cell measures the force applied to the Cartridgepiston by the piston actuator. The load cell is a compression type donutload cell that uses strain gauge circuitry to produce analogmeasurements.

A solenoid-operated oxygen valve controls the flow of oxygen from theoxygen supply to the Cartridge. The valve is normally closed. The valveis pulsed open in feedback with the oxygen pressure transducer tomaintain the oxygen pressure in the cartridge at the desired set point(of approximately 550 psi).

As discussed above, the Cartridge Housing has solenoid-operatedactuators that control the cartridge needle valves, vent valves, anddoor lock actuator. Five valves within the oxygenation cartridge 2100are controlled by three needle valve actuators and two vent valveactuators. Each valve actuator mechanism has a pin on one end of a leverand a pull-type solenoid on the other. The oxygen vent valve has aspring that pushes the pin away from the vent valve to maintain thevalve open when the solenoid is not energized. For the other fourvalves, a spring preloads the lever, pushing the pin against thecartridge needle valve or vent valve to maintain the valve closed whenthe solenoid is not energized. When energized, the solenoid pulls thepin away from the needle or vent valve, allowing the valve to open frompressure inside the cartridge. The door lock has a spring that engagesthe lock mechanism when the solenoid is not energized.

The Fluid Pump Assembly

Referring again to FIG. 1, the Cartridge Control subsystem 2001 includesa fluid pump assembly 2010, which brings together the fluid pump 2011,the combination bubble-detector/flow meter 2060, the draw tube 2020, thereturn tube 2030, and the return safety clamp 2070 to modulate fluidflow through the system.

When the system is used in SSO₂ therapy, the fluid pump withdrawsarterial blood from the patient and pumps it through the oxygenationcartridge 2100 and the infusion catheter back to the patient (see FIG.23). The fully occlusive peristaltic blood pump 2011 interfaces with thecartridge tubing and thus does not have direct fluid contact. The systemuser inserts the draw side tubing 2020 into the pump head and the returnside tubing 2030 into the flow probe during system set-up. FIGS. 9 and10 show the visible components of the blood pump 2011.

The pump head 2012 is coupled to the DC motor mounted inside theenclosure of the mid-section control module. The pump head 2012 and thecombination bubble detector/flow meter 2060 are mounted on the front ofthe module enclosure. The blood pump 2011 operates at a fixed flow rateof 75 ml/min, set by software. The blood pump supports the 75 ml/minflow rate set point at hydrodynamic pressures less than or equal to 35psig. Component features of the blood pump include: pump head 2012, pumphead detector 2013, pump motor 2014, and pump lock 2015.

The pump head 2012 is a three-roller peristaltic pump head mounted onthe front of the system main enclosure. The occlusion setting is fullyocclusive for the tubing, so the pump head 2012 functions as a tubingclamp when stopped. The peristaltic pump features an over-center,cam-actuated mechanism with a handle 2016 to facilitate loading oftubing. The pump head shaft is coupled to the blood pump DC motor.

The blood pump 2011 has a sensor to detect if the pump head is closed.This IR sensor detects a reflective feature when the pump head is in theclosed position and provides an electrical signal to the controller2080. The pump motor 2014 will not turn when the pump head 2012 is inthe open position.

The blood pump motor 2014 assembly is a DC servomotor with opticalencoder and gearbox. The motor speed is regulated by the cartridgecontroller PCB using Pulse Width Modulation (PWM). This circuit providesconsistent pump speed operation independent of load, line voltage andtemperature variations. The controller PCB uses an analog input from theblood flow measurement to maintain the flow rate set point, and sendsthis analog signal to the Safety Interlock. The pump motor shaft has anoptical encoder with a revolution index output that is measured by thecontroller PCB.

The blood pump incorporates a custom locking mechanism which only opensto allow loading or unloading of draw tubes. This prevents inadvertentopening of the pump head during operation.

FIG. 11 illustrates an exemplary locking mechanism in accordance withthe present invention. In the present preferred embodiment, the pump hasa pump lever 2016 connected to an off-center cam 2018. When the lever2016 is placed in the open position, the cam blocks the pump lock latch2017 so the lock cannot be engaged. When the lever is placed in theclosed position, the cam is rotated out of the way so that the pump locklatch 2017 can be fully engaged. Once the latch 2017 is engaged, itblocks the cam so that the lever cannot be rotated into the openposition, thereby, preventing accidental opening of the pump head oncethe lock is engaged.

Combination Bubble-Detector/Flow Meter

The bubble detector/flow meter 2060 is a combination device whichperforms both the functions of bubble detection and flow measurement. Asshown in FIGS. 1, 2, 9 and 10 of the present preferred embodiment, thecombination bubble detector/flow meter 2060 is an ultrasonic devicemounted on the mid-section control module, and is coupled to the returntube 2030. The bubble detector/flow probe 2060 communicates with adigital signal processor (DSP) on the controller PCB to continuouslymonitor the return blood path for air bubbles. The DSP has software thatcounts and calculates the size of each bubble that passes through thereturn tubing. The bubble detection function of the combination detector2060 is capable of counting individual bubbles as small as 100-μm indiameter. The bubble detector DSP software also calculates a cumulativebubble volume. If the cumulative bubble volume reaches 10 μl during the90-minute treatment, or signal strength is out of range, the BubbleDetector initiates a system shutdown. Measurement of bubble uses atime-of-flight measure which compensates for environmental variances.

In the present preferred embodiment, the ultrasonic probe has a pair ofcrystals oriented across the fluid path at a 45-degree angle. The signalcan be sent in either direction, but one direction is upstream and theother is downstream. After data has been collected by the DataCollection State Machine, the difference in the upstream and downstreamdata is used to calculate the fluid flow. The flow rate is calculated onthe difference between the two measured phases of the collected data.

The flow rate is proportional to the differences between the two phaseangles as depicted in FIG. 5, so time-of-flight measurements can be doneby calibrating the phase angle differences against a known flow ratefirst and then using the proportionality to determine other flow rates.Detection range can be in the range of about 1-200 ml/min.

The bubble detector/flow probe digital signal processor (DSP) processsignals received from the bubble detector/flow meter transduceraccording to its software. Software algorithms in the DSP measure theelectrical signal attenuation that occurs when a bubble passes throughthe transducer. The bubble size is proportional to the magnitude of theattenuation. The DSP feeds input to the cartridge controller which hassoftware algorithms to count bubbles and calculate the accumulatedbubble volume. The bubble detector DSP provides serial communication tothe cartridge controller for accumulated bubble volume, andsends/receives digital signals to/from the safety interlock.

FIG. 25 is a block diagram illustrating the algorithm in accordance withthe present invention for flow calculation. The procedure to calculatethe flow rate first calculates the upstream and downstream phases byrunning a phase lock loop algorithm against the sampled data. The phaselock loop calculates the in phase and quadrature phase signalamplitudes, and then forces the quadrature phase value to zero. Theoutput of the phase lock loop is the phase angle that it takes to keepthe in phase signal peaked against the input data. The differencebetween the phase angle is calculated, and a calibration offset isadded. The calibrated flow measurement is then passed through a low passfilter for clean up.

FIG. 26 is a block diagram illustrating the algorithm in accordance withthe present invention for bubble detection. The bubble detection processinvolves calculating the upstream and downstream signal amplitudes andaveraging them, checking the signal level against a lower limitthreshold, peak detecting the signal, and determining the end of bubblestate.

The peak detector is first checked for signal above the noise threshold.Once a signal has been detected, the sample by sample peak iscalculated. A peak is qualified when either the signal drops below thenoise threshold, or reaches a relative minimum and then rises above therelative minimum plus the noise threshold. The peak detection scheme isdesigned to respond to bubbles that are closely spaced, or evenoverlapping in the sensor.

Once a bubble peak has been captured the resulting peak is first scaledto reflect a normalized area, because the measured ultrasonic signalattenuation is proportional to the projected 2-D area of the bubble. Thearea is then divided by PI (π) and the square root is taken resulting inthe radius. The radius is then multiplied by the scaled area and then by4/3 to generate the bubble volume. Individual bubble volumes are addedto generate the accumulated bubble volume. The accumulated bubble volumeis then passed up to the host system for further processing.

Referring again to FIG. 2A, a return safety clamp 2070 for isolating thepatient from blood flow in the Cartridge in the event of a faultcondition is mounted on the mid-section main control module and coupledto the return tube 2030. The Cartridge Controller subsystem 2001provides the drive electronics to actuate the return clamp. This pinchclamp is normally closed. The cartridge tubing is normally loaded by theuser into these clamps during initial system set-up.

The Oxygenation Cartridge (The Gas-Enrichment Device)

In the present preferred embodiment, the Gas-enrichment device is in theform of a Cartridge, as shown FIG. 13. The Cartridge 2100 is asingle-use disposable device that is designed to be loaded into thesystem. The Cartridge has a three-chambered body that creates SSO₂solution from inputs of hospital-supplied oxygen and physiologic saline,and mixes the SSO₂ solution with arterial blood within the Cartridgeblood path. The Cartridge has a tube set that draws the patient'sarterial blood through the draw line, and returns oxygen-supersaturatedblood through the return line to the infusion catheter. The Cartridgedraw line connects to an arterial sheath. Sheath placement may becoaxial (single arterial access site) or contralateral (two arterialaccess sites) at the physician's discretion. A physician makes two lineconnections during the initiation of SSO₂ therapy: the Cartridge drawline 2020 is attached to the arterial sheath before priming the bloodflow path, and the return line 2030 is attached to the infusion catheterafter the blood flow path is successfully primed.

FIG. 14 shows a schematic illustration of the three-chambered structureof the oxygenation Cartridge 2100, which includes the physiologic fluidchamber 2103, the atomization chamber 2105, and the mixing chamber 2106.In operation, saline is drawn from the IV bag into the physiologic fluidchamber 2103, and then pumped into the pressurized atomization chamber2105. Oxygen is supplied from an oxygen tank and introduced into theatomization chamber 2105, mixing with the atomized saline to form anoxygen-supersaturated physiologic fluid. This oxygen-rich saline is thenintroduced into the mixing chamber 2106 to be mixed with blood. Theblood is drawn into the mixing chamber 2106 through the draw line. Oncethe blood is mixed with the oxygen-rich saline, the mixture is thenreturned to the patient through the return line.

As shown in FIGS. 8 and 9, the Cartridge housing 2050 has a door 2051and grooves for fitting the draw tube 2020 and return tube 2030. TheCartridge Housing 2050 works in conjunction with the Cartridge 2100during operation. It has a motorized piston actuator that operates theCartridge piston and delivers saline from an IV bag. The CartridgeHousing 2050 also has a set of needle value actuators to control theflow of liquid through the Cartridge, and vent valve actuators todepressurize the Cartridge oxygen chamber and blood mixing chamber.

FIGS. 8 and 9 show the configuration in which the Cartridge 2100 isloaded in the Cartridge Housing 2050.

FIG. 10 illustrates the location of the pump assembly 2010 in relationto the Cartridge Housing 2050.

Referring to FIGS. 14 and 15, during operation, a tube is coupled to theIV bag to provide saline. The outer end of the tube is coupled to a porton the oxygenation cartridge 2100, forming a passageway that leads tothe fluid supply chamber. A check valve 2102 is disposed in the fluidpassageway 2151 so that fluid may enter the fluid chamber 2103 throughthe fluid passageway 2151, but fluid cannot exit through the fluidpassageway.

FIG. 15 further illustrates a detailed view of the check valve 2102.Referring to the figure, the check valve 2102 has an O-ring seal 2152that is disposed between a counter bore in the fluid passageway 2151 andthe port. A spring 2154 biases a ball 2153 into contact with the O-ringseal 2152. When fluid moving in the direction of the arrow overcomes theforce of the spring and the pressure within the fluid supply chamber,the ball is pushed against the spring so that fluid may flow into thefluid supply chamber. The flow of fluid is unidirectional because theball efficiently seals against the O-ring seal.

Referring again to FIG. 14, a piston assembly 2104 is located at theopposite end of the fluid supply chamber from the check valve. Asillustrated in greater detail in FIG. 16, the piston assembly 2104 ismoveable between a first position (left figure) and a second position(right figure). A key is provided at the free end of the pistonassembly. The key includes a narrow portion and a relatively widerportion so that it somewhat resembles a doorknob, thus allowing a deviceto latch onto the ram of the piston actuator assembly and move itbetween the first and second position.

Referring back again to FIG. 14, the fluid supply chamber 2103 has asecond fluid passageway that is coupled to a fluid passageway by a tube.The passageway is an inlet to a valve assembly that controls the mannerin which fluid from the fluid supply chamber is delivered into theatomization chamber.

In operation, the piston assembly 2104 within the fluid supply chamberacts as a piston pump. As the piston 2161 retracts, fluid is drawn intothe chamber from the fluid supply. No fluid can be drawn from passagewaybecause valve assembly is closed and a check valve is closed in thisdirection. As the piston 2161 extends, the fluid within the chamber ispressurized, typically to about 650 psig, and expelled from the fluidsupply chamber through the fluid passageway. The outlet of the fluidsupply chamber is coupled to an inlet of the atomization chamber via anappropriate fluid passageway.

The valve assembly includes three valves: a fill valve 2202, a flushvalve 2203, and a flow valve 2204. The system uses needle valves thatare normally biased in the closed position as shown in FIG. 17. When thepressure exerted on the needle rises above a certain level, such asabout 100 psi and the system actuator is open, the valves will move fromthe closed position to the opened position, assuming that they areallowed to do so. Push pins and associated actuation mechanisms maintainthe valves in the closed positions until one or more of the valves is tobe opened.

Oxygen is delivered under pressure to the atomization chamber via apassageway. The oxygen supply is coupled to the inlet of the passagewayto provide the desired oxygen supply. If all of the valves are closed,fluid flows from the inlet passageway into a passageway in which thefill valve 2202 is located. Because the cross-sectional area of thepassageway is larger than the cross-sectional area of the fill valve2202, the fluid flows around the closed fill valve and into a passagewaythat leads to an atomizer.

The atomizer includes a central passageway in which a one-way valve isdisposed. The one-way valve is a check valve similar to that describedwith reference to FIG. 15. Accordingly, when the fluid pressureovercomes the force of the spring in the one-way valve and overcomes thepressure of the oxygen within the atomizer chamber, the fluid travelsthrough the passageway and is expelled from a nozzle 2108 at the end ofthe atomizer.

The nozzle 2108 forms fluid droplets into which the oxygen within theatomization chamber diffuses as the droplets travel within theatomization chamber. This oxygen-enriched fluid is referred to assupersaturated oxygen (SSO₂) solution. The nozzle forms a droplet conedefined by the angle a, which is typically about 20 degrees to about 40degrees at normal operating pressures, e.g., about 550 psig, within theatomization chamber. The nozzle is preferably a simplex-type, swirledpressurized atomizer nozzle including a fluid orifice of about 0.004inches diameter to 0.005 inches diameter. The droplets infused with theoxygen fall into a pool at the bottom of the atomizer chamber. Since theatomizer will not atomize properly if the level of the pool rises abovethe level of the nozzle, the level of the pool is controlled to ensurethat the atomizer continues to function properly.

By design, oxygen is dissolved within the atomized fluid to a muchgreater extent than fluid delivered to the atomizer chamber in anon-atomized form. As previously stated, the atomization chambertypically operates at a constant pressure of about 550 psig. Operatingthe atomizer chamber at 550 psig, or any pressure above 200 psigpromotes finer droplet formation of the physiologic solution from theatomizer and better saturation efficiency of the gas in the physiologicfluid than operation at a pressure below 200 psig.

The oxygen-supersaturated fluid formed within the atomizer chamber 2105is delivered to the mixing chamber 2106 where it is combined with theblood from the patient. Because it is desirable to control the extent towhich the patient's blood is enriched with oxygen, and to operate thesystem at a constant blood flow rate, it may be desirable to dilute theoxygen-supersaturated fluid within the atomizer chamber to reduce itsoxygen content. When such dilution is desired, the fill valve is openedto provide a relatively low resistance path for the fluid as compared tothe path through the atomizer. Accordingly, instead of passing throughthe atomizer, the fluid flows through a passageway which extendsupwardly into the atomizer chamber via a tube. The tube isadvantageously angled somewhat tangentially with respect to thecylindrical wall of the atomizer chamber so that the fluid readily mixeswith the oxygen-supersaturated fluid in the pool at the bottom of theatomizer chamber.

The valve assembly essentially performs two additional functions. First,with the fill valve and the flow valve closed, the flush valve may beopened so that fluid flows from the inlet passageway can pass through aseries of passageways, the latter of which has a cross-sectional arealarger than the cross-sectional area of the flow valve. Thus, the fluidflows out of an outlet passageway that is coupled to a capillary tube2109 (FIG. 18). The capillary tube terminates in a tip that extendsupwardly into the mixing chamber. Since this fluid has not beengas-enriched, it essentially serves to flush the passageways and thecapillary tube to remove any contaminants and to ensure adequate fluidflow. Second, with the fill valve and the flush valve closed, the flowvalve may be opened when it is desired to deliver the gas-supersaturatedfluid from the pool at the bottom of the atomizer chamber into themixing chamber.

In this second circumstance, the gas-supersaturated fluid readily flowsfrom the atomization chamber through the capillary tube and into themixing chamber due to the fact that pressure within the atomizationchamber is relatively high, e.g., approximately 550 psig, and pressurewithin the mixing chamber is relatively low, e.g., about 30 psia. Theend of the capillary tip is positioned below a blood inlet of the mixingchamber. This spacial arrangement typically ensures that the bloodflowing through the draw tube and into the blood inlet effectively mixeswith the oxygen-supersaturated fluid flowing into the mixing chamberthrough the capillary tip. Finally, by the force of the blood pumpsystem, the oxygenated blood is pumped out of the mixing chamber throughan outlet into the return tube.

Typically, the capillary tube 2109 and the capillary tip are relativelylong to ensure that proper resistance is maintained so that the oxygenwithin the oxygen-supersaturated fluid remains in solution as it travelsfrom the atomization chamber into the mixing chamber. The capillary tubeand the tip are in the range of 50 microns to 300 microns in length andin the range of 3 inches to 20 inches in internal diameter. To maintainthe compact size of the oxygenation device, therefore, the capillarytube is wrapped about the exit nozzle of the mixing chamber, asillustrated in the detailed drawing of FIG. 18. To protect the coiledcapillary tube from damage, a protective shield is advantageously formedaround the coiled capillary tube to create a compartment.

Both the atomization chamber 2105 and the mixing chamber 2106 includevent valves 2200. The vent valves, as illustrated in the detail drawingof FIG. 19, are one-way valves that allow gas pressure to be vented outof the Cartridge and into the atmosphere. The vent valves include a ballor piston head 2206 that is biased in a closed position against anO-ring seal 2202 by a spring 2201. The biasing force is light so thatonly 1 to 2 psi within the respective chambers is sufficient to move theplunger away from the seal to vent the chamber. Therefore, actuationdevices that are part of the cartridge housing and controlled by thesystem controller normally maintain the valves in the closed position.

As previously mentioned, the Cartridge may optionally include aninformation recording element for recording data relevant to aprocedure, such as flow time, desired concentration, etc. The recordingelement may be any suitable information recording device such as a barcode label, an RFID chip, a PROM, a flash memory, or any other suitablememory device commonly used in the art. The information recordingelement may also be used to record relevant patient information such aspatient health information (e.g., age, sex, weight, height, etc.),procedural data, and specific system setup information tailored to thereceiving patient's treatment plan. Inclusion of such informationfurther enhances operator convenience and patient safety.

When information recording elements are included in the cartridge, thesystem may further include corresponding means for retrieve andutilizing the information. For example, if a bar code label is used, thesystem may further include a bar code reader. The on-board cartridgecontroller may further include an internal database or be connected toan external information system for retrieving information correspondingto the bar code. When the information includes operating parameters suchas treatment duration, temperature, concentration, flow rate, etc., theymay be automatically utilized by the system controller.

Alternatively, the information retrieving means may be a separatestand-alone system to be used in conjunction with the oxygenation systemof the present invention. For example, a stand-along bar code reader maybe used to read the bar code on the cartridge by the operator prior toinserting the cartridge into the system.

Cartridge Valve Actuation

The size and shape of the oxygenation Cartridge 2100, the contour of theCartridge Housing 2050, and the closing of the door 2051 ensure that theCartridge is positioned in a desired manner within the Cartridge Housing2050. Correct positioning is important due to the placement of thevalves and vents of the Cartridge 2100 and the manner in which they arecontrolled and actuated. The valves and vents of the Cartridge areactuated using pins. The top of the Cartridge includes two vents, andthe bottom of the Cartridge includes three valves. These vents andvalves are electromechanically actuated using solenoid-actuated pins.

A detailed view of these actuation devices is illustrated in FIGS. 20and 21. Referring first to FIG. 20, a bottom view of the CartridgeHousing is illustrated. It should be noted that the bottom portion ofthe Cartridge Housing includes a slot through which the blood returntube from the oxygenation Cartridge may pass. Once the oxygenationCartridge 2100 is in place within the Cartridge Housing 2050, the fillvalve 2203, the flush valve 2204, and the flow valve 2205 should be inalignment with respective actuation pins 2057. Each of the pins istapered at the end to provide an increased tolerance for misalignment.Each of the actuation pins is moved between a closed position and anopen position by a respective solenoid 2058. Each of the solenoids iscoupled to its respective actuation pin and actuated via a respectivelever 2059. Each of the respective levers pivots on a respective fulcrumor pivot pin.

The manner in which the actuators operate may be understood withreference to the cross-sectional views of FIG. 20. The valves arenormally held in a closed position. As illustrated in FIG. 20, a pistonis urged into an extended position by a spring that biases one end ofthe lever.

To allow the flush valve 2204 to open, the pin is actuated asillustrated in FIG. 21. The actuation of the solenoid moves the pistongenerally into a retracted position. The force of the solenoid overcomesthe bias of the spring and moves the actuation pin. With the actuationpin in a retracted position, the flush valve 2204 may open.

The oxygen vent valve is normally open and the mixing chamber vent valveis normally closed. Referring now to FIG. 21, a top view of thecartridge housing 2050 is illustrated. The top portion of the cartridgeHousing also includes a slot through which the IV tube may pass. Oncethe cartridge 2100 is properly positioned within the cartridge housing2050, the vent valves 2200 align with actuation pins, respectively. Thepins are also tapered at the ends to increase tolerance to misalignment.Each of the actuation pins is actuated by a respective solenoid. Each ofthe solenoids is coupled to the respective actuation pins and actuatedby a respective lever. Each of the levers pivots about a fulcrum orpivot pin, respectively.

To open the vent valves 2200, the solenoids are actuated. As illustratedin FIG. 21, when the solenoid is actuated, the piston moves into aretracted position. The force of the solenoid overcomes the biasingforce of the spring and, thus, the lever moves the actuation pin into aclosed position. When the actuation pin is in the retracted position,the vent valve may move upwardly to open and vent gas within the mixingchamber.

The Infusion Catheter

FIG. 22 shows an exemplary infusion catheter of the present preferredembodiment. The catheter generally is a sterile, single-useover-the-wire device that may be inserted into patients throughcommercially available guide catheters 6 F or larger. The catheter'souter diameter (O.D.) is preferably 4.6 French (F) from the distal tipto the proximal strain relief 4015. The catheter is extruded in acontinuous process that transitions from soft tip to the stifferproximal shaft. The nominal usable length is 127 cm and the nominaloverall length of the catheter is 135 cm. The inner diameter (I.D.) ofthe single lumen end-hole catheter is nominally 0.046 in except at thelocation of the platinum/iridium radiopaque marker band 4020. The I.D.under the marker band is a minimum 0.037 in.

Components of the infusion catheter may include: Luer hub 4010, strainrelief 4015, and proximal shaft 4020.

The Luer hub 4010 is a female hub molded over the proximal O.D. of theshaft. The luer hub 4010 enables attachment of the cartridge returntubing to the catheter. A polyolefin strain relief 4015 is applied overthe shaft and luer hub 4010 joint with a heat shrinking process.

The infusion catheter preferably has a non-plasticized whitehigh-density polyethylene (HDPE) proximal shaft. The draw tubingconnects to the same femoral arterial sheath that may be used forangioplasty and stenting procedures. Sheath placement may be coaxial (inone femoral artery) or contralateral (in both the right and left femoralarteries), at the physician's discretion. FIG. 23 illustrates howarterial blood is withdrawn via the sidearm through the annular spacebetween the guide catheter and sheath; in this configuration (coaxial),a single 8 F introducer sheath can be used. The draw tubing luer fittingconnects to the sidearm. The infusion catheter is placed through the 6 Fguide catheter over a guidewire, to the desired target location within acoronary artery. The guidewire is removed prior to initiation of bloodflow. When extracorporeal blood flow is initiated, the infusion catheterand the return tubing are wet-connected to ensure that no gaseous emboliare introduced to the patient during priming. The term ‘wet connection’requires that both devices are fully blood-primed and free of trappedair bubbles. The cartridge return tubing luer fitting connects to theluer hub 4010 of the infusion catheter 4000. For the contralateralapproach (not shown), a 5 F introducer sheath is used on the draw side,while a 6 F introducer sheath provides access for the 6 F guidecatheter. This alternative approach may be used by physicians who preferto use two smaller sheaths for arterial access (5 F and 6 F) instead ofa single 8 F sheath.

Priming the Fluid Path

As discussed above, the Cartridge of the present preferred embodimenthas a three-chambered body. Referring to FIG. 14, the Cartridge 2100,when loaded into the Cartridge Housing enclosure 2050, form a numberfluid pathways, notably the extracorporeal circuit pathway, whichconducts bodily fluid from the patient through the draw line into themixing chamber, and then returning the bodily fluid to the patient viathe return line, and the physiologic fluid pathway, which draws thephysiologic fluid from the physiologic fluid source into the physiologicfluid chamber to be pressurized and transmitted to the atomizing chamberand then directed into the mixing chamber to be mixed with the bodilyfluid. Prior to using the system and the Cartridge, the various segmentsof the fluid paths must be primed with an appropriate fluid.

The physiologic fluid supply chamber 2103 and the atomizing chamber 2105should be properly primed with the physiologic fluid before beginning ofSSO₂ administration, whereas the draw line, the mixing chamber, and thereturn line should be properly primed with the bodily fluid before SSO₂administration. It is an advantageous feature of the present inventionthat these priming steps are automated by the Cartridge Controller. Thegenerally steps of priming the fluid pathways are outlined as follows:

When the Cartridge is properly loaded into the Cartridge Housingenclosure 2050, and the door 2051 is closed, the system automaticallybegins the preparatory steps of priming the appropriate Cartridgechambers with the physiologic fluid. During this stage, the systemdisplays a progress message on the display to indicate that preparatoryprocedures are in progress. During the preparatory procedures, thesystem also performs a series of diagnostic checks to ensure that theCartridge and the system are operating normally. Once the system isfinished with the initial preparatory procedures, a message is displayedto indicate to the user that priming of the extracorporeal circuit maybe initiated.

The user may then connect the extracorporeal circuit by mounting thedraw tube in position through the pump head and connected to the patientvia a catheter. The return tube is also mounted in position through thecombination bubble detector/flow meter 2060 and the return clamp 2070.At this stage, the return clamp 2070 is closed tight to effectively sealoff any fluid from exiting the return tube. These steps may be performedeither while the system is performing the initial preparatory steps, orafter the system indicates that initial preparatory steps are completed.

Once the system has completed the initial preparatory steps and the userhas connected the extracorporeal circuit, the user may then beginpriming the extracorporeal circuit by pressing the “priming switch” 3040next to the display. It is an advantageous feature of the presentinvention that the extracorporeal path priming is automated withbuilt-in safety checks without requiring user intervention. During thefirst stage of extracorporeal circuit priming, bodily fluid is drawninto the mixing chamber through the draw line while the return clamp2070 and the vent valve 2107 of the mixing chamber are held closed. Asthe bodily fluid fills the chamber, hydrostatic pressure will build upin the pathway to verify that all components are properly connected withno leakage in the pathway. The pressure transducer monitors the changein pressure. When a proper pressure is reached (approximately 5 psi),the vent value is opened to allow excess gas to escape. The level sensorin the mixing chamber continues to monitor the level of the bodily fluidin the chamber until the fluid has reached a level appropriate formixing action to commence. At this point, the return clamp is releasedand the fluid is allowed to exit the return tube.

After a small amount of bodily fluid has exited the return tube toestablish a constant flow rate and pressure, the user verifies that novisible bubble is present in the exiting fluid. Then, the user makeswet-to-wet connection between the return tube and the infusion catheterto complete the extracorporeal circuit.

In this way, bubble formation is minimized as a result of the fluidpathway design and the priming procedures. No independent or externalbubble eliminator is needed in a system of the present invention.

Although the present invention has been described in terms of specificexemplary embodiments and examples, it will be appreciated that theembodiments disclosed herein are for illustrative purposes only andvarious modifications and alterations might be made by those skilled inthe art without departing from the spirit and scope of the invention asset forth in the following claims.

1. A gas enrichment system having an extracorporeal circuit forenriching a bodily fluid of a patient with a gas-enriched fluid,comprising: an enclosure configured for receiving a gas-enrichmentdevice, wherein said gas-enrichment device comprises a gas-enrichmentchamber for enriching a physiologic fluid with the gas and a mixingchamber for mixing the gas-enriched physiologic fluid with the bodilyfluid of the patient; a pumping assembly comprising a pump forcontrolling fluid flow through the extracorporeal circuit; and acontroller for automatic control of gas-enrichment and extracorporealcircuit operations, wherein said system and said gas-enrichment device,when loaded into the system, provide a fluid path for the bodily fluidto circulate from the patient to the mixing chamber and back to thepatient, and wherein said controller is capable of controlling thepumping assembly and the gas-enrichment device to perform an automatedpriming sequence to prime the gas-enrichment chamber with thephysiologic fluid upon loading the gas-enrichment device, and to primethe fluid path with the bodily fluid upon receiving a priming commandfrom the user, wherein said system is configured and programmed to buildup and monitor a pressure in the extracorporeal circuit before theestablishment of a predetermined fluid level in the mixing chamberduring priming to verify proper loading of the circuit, wherein thepressure is higher than the one that can be built up by theestablishment of the fluid level.
 2. The system of claim 1, wherein saidfluid path leading from the mixing chamber to the patient having a nonturbulent fluid flow geometry.
 3. The system of claim 1, wherein saidmixing chamber is capable of functioning as a bubble trap in the fluidpath.
 4. The system of claim 1, wherein said mixing chamber has a firstinlet operatively connected to a tubing for directing the bodily fluidinto the mixing chamber, a second inlet operatively connected to thegas-enrichment chamber for receiving the gas-enriched physiologic fluid,a first outlet for allowing excess gas to escape so as to set fluidlevels in the chamber, and a second outlet for allowing fluid to exitthe mixing chamber.
 5. The system of claim 4, wherein saidgas-enrichment device further comprising one or more level sensors, andwherein when said gas-enrichment device is loaded into the system: saidmixing chamber is operatively connected to a draw tube and a returntube; said draw tube is operatively coupled to a unidirectional pumpcapable of variable speed and completely occluding fluid flow in thefluid path; said return tube is coupled to a return clamp configured tocompletely stop fluid flow in the return tube when closed.
 6. The systemof claim 5, wherein: said gas-enrichment device further comprising oneor more pressure transducer(s) capable of monitoring pressure in theextracorporeal circuit; said first outlet, return clamp and pressuretransducers are configured to work together in verifying proper loadingof the tubes during priming; and said first outlet is a vent, which isclosed first during priming when verifying proper loading of the tubes,and then opened for allowing excess gas to escape so as to set fluidlevels in the chamber until the mixing chamber is primed.
 7. The systemof claim 1, wherein said gas-enrichment device further comprising one ormore level sensors, and wherein when said gas-enrichment device isloaded into the system: said mixing chamber is operatively connected toa draw tube and a return tube; said draw tube is operatively coupled toa unidirectional pump capable of completely occluding fluid flow in thefluid path; said return tube is coupled to a return clamp configured tocompletely stop fluid flow in the return tube when closed; and saidautomated priming sequence further comprises a sequence of steps toverify proper loading of the extracorporeal circuit, comprising:maintaining the return clamp and the first outlet of the mixing chamberin close state; drawing the bodily fluid into the mixing chamber tobuild up pressure in the mixing chamber so as to verify that thegas-enrichment device is properly loaded and that no leakage is presentin the fluid path; and opening the return clamp only when apredetermined fluid level has been established in the mixing chamber. 8.The system of claim 7, wherein said automated priming sequencecomprises: loading the gas-enrichment device into the system; primingthe physiologic chamber and the gas-enrichment chamber with aphysiologic fluid; and priming the extracorporeal circuit by effectingthe bodily fluid to flow through the circuit, wherein the bodily fluidenters the circuit from the draw tube, flows into the mixing chamber andthen exits through the return tube, wherein said step of priming thephysiologic chamber and the gas-enrichment chamber is performed by thesystem automatically upon loading of the gas-enrichment device, andwherein said priming the extracorporeal circuit step is performed whenthe system receives a priming command from a user.
 9. A gas-enrichmentsystem having an extracorporeal circuit for enriching a bodily fluid ofa patient with a gas-enriched fluid, comprising an enclosure configuredfor receiving a gas-enrichment device, wherein said gas-enrichmentdevice comprises a gas-enrichment chamber for enriching a physiologicfluid with the gas and a mixing chamber for mixing the gas-enrichedphysiologic fluid with the bodily fluid of the patient; a pumpingassembly comprising a pump for controlling fluid flow through theextracorporeal circuit; a controller for automatic control ofgas-enrichment and extracorporeal circuit operations; one or more loadcells configured to monitor the pressure within the extracorporealcircuit; and a memory device for storing pump, oxygen and cartridgeoperating parameters, wherein said system and said gas-enrichmentdevice, when loaded into the system, provide a fluid path for the bodilyfluid to circulate from the patient to the mixing chamber and back tothe patient, wherein said system is configured and programmed to buildup and monitor a pressure in the extracorporeal circuit before theestablishment of a predetermined fluid level in the mixing chamberduring priming to verify proper loading of the circuit, wherein thepressure is higher than the one that can be built up by theestablishment of the fluid level.
 10. A method for priming theextracorporeal gas-enrichment system in claim 1 useful for enriching abodily fluid of a patient with a gas-enriched fluid, wherein said systemcomprises an enclosure configured for receiving a gas-enrichment device,and wherein said gas-enrichment device comprises a physiologic fluidchamber, a gas-enrichment chamber, and a fluid mixing chamber, the fluidmixing chamber having: a first inlet operatively connected to a drawtube for receiving the bodily fluid from a patient; a second inlet forreceiving a gas enriched fluid; a first outlet for releasing gas fromthe chamber; a second outlet operatively connected to a return tube forallowing the gas-enriched bodily fluid to exit the chamber, wherein saidreturn tube is coupled to a return clamp capable of stopping fluid flowin the return tube when closed; one or more level sensors for monitoringfluid levels in the chambers; and one or more pressure transducer formonitoring the pressure in the extracorporeal circuit, the methodcomprising the steps of: loading the gas-enrichment device into thesystem; building up and monitoring a pressure in the extracorporealcircuit before the establishment of a predetermined fluid level in themixing chamber, wherein the pressure built up is higher than can bebuilt up by establishment of the fluid level, priming the physiologicchamber and the gas-enrichment chamber with a physiologic fluid; andpriming the extracorporeal circuit by effecting the bodily fluid to flowthrough the circuit, wherein the bodily fluid enters the circuit fromthe draw tube, flows into the mixing chamber and then exits through thereturn tube, wherein said step of priming the physiologic chamber andthe gas-enrichment chamber is performed by the system automatically uponloading of the gas-enrichment device, and wherein said priming theextracorporeal circuit step is performed when the system receives apriming command from a user.
 11. The method of claim 10 furthercomprising a sequence of steps for verifying proper loading of thegas-enrichment device, wherein said sequence of steps comprising:closing the return clamp and the first outlet prior to drawing thebodily fluid into the mixing chamber; introducing the bodily fluid intothe mixing chamber while holding the return clamp and the first outletclosed so as to build up pressure in the circuit; verifying properloading of the gas-enrichment device by monitoring inputs from thepressure transducer and the level sensor(s); opening the first outlet toallow excess gas to escape and the bodily fluid to rise; monitoring thelevel of the bodily fluid in the mixing chamber; and opening the returnclamp to allow flow of the bodily fluid through the return tube when thelevel of the bodily fluid reaches a minimum level necessary for mixing.12. The method of claim 11 further comprising a step of stopping thesystem when the gas-enrichment device is not properly loaded.
 13. Thesystem of claim 1, wherein said pressure is about 5 psi.
 14. The systemof claim 9, wherein said pressure is about 5 psi.